김지현 (서울대학교 의과대학)

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서울대학교 의과대학

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Sci. Adv., Dec 22 2023, 9 (51) | https://doi.org/10.1126/sciadv.adi3770 JAK3 inhibitor suppresses multipotent ILC2s and attenuates steroid-resistant asthma

Jihyun Kim ^{1 2}, Jongho Ham ^{1 2 3}, Hye Ryun Kang ^{2 4}, Yong-Soo Bae ^{3 5}, TaeSoo Kim ⁶, Hye Young Kim ^{1 2 3 *}

¹Laboratory of Mucosal Immunology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, South Korea.

²Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, South Korea.

³Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Suwon, South Korea.

⁴Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea.

⁵Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea.

⁶Department of Life Science, Multitasking Macrophage Research Center, Ewha Womans University, Seoul, South Korea.

^*Corresponding author: correspondence to Hye Young Kim

Abstract

Steroids are the standard treatment for allergic airway inflammation in asthma, but steroid-refractory asthma poses a challenge. Group 2 innate lymphoid cells (ILC2s), such as T helper 2 (T_H2) cells, produce key asthma-related type 2 cytokines. Recent insights from mouse and human studies indicate a potential connection between ILC2s and steroid-resistant asthma. Here, we highlight that lung ILC2s, rather than T_H2 cells, can develop steroid resistance, allowing them to persist and maintain their disease-driving activity even during steroid treatment. The emergence of multipotent IL-5⁺IL-13⁺IL-17A⁺ ILC2s is associated with steroid-resistant ILC2s. The Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT) 3, 5, and 6 pathways contribute to the acquisition of steroid-resistant ILC2s. The JAK3 inhibitor reduces ILC2 survival, proliferation, and cytokine production in vitro and ameliorates ILC2-driven Alternaria-induced asthma. Furthermore, combining a JAK3 inhibitor with steroids results in the inhibition of steroid-resistant asthma. These findings suggest a potential therapeutic approach for addressing this challenging condition in chronic asthma.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-12-21)
연구진국내 연구진
분야 의약학 > 면역의학

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